Population kinetic/pharmacodynamic modelling of the haemodynamic effects of cafedrine/theodrenaline (Akrinor) under general anaesthesia.

AIMS: The 20:1 combination of cafedrine and theodrenaline (C/T) is widely used in Germany for the treatment of arterial hypotension. Since there is little knowledge about the impact of covariates on the effect, the aim was to develop a kinetic/pharmacodynamic covariate model describing mean arterial pressure (MAP), systolic (SBP) and diastolic blood pressure (DBP), and heart rate (HR) for 30 min after the administration of C/T. METHODS: Data of patients receiving C/T from the HYPOTENS study (NCT02893241, DRKS00010740) were analysed using nonlinear mixed-effects modelling techniques. RESULTS: Overall, 16 579 measurements from 315 patients were analysed. The combination of two kinetic compartments and a delayed effect model, coupled with distinct Emax models for HR, SBP and DBP, described the data best. The model included age, sex, body mass index (BMI), antihypertensive medication, American Society of Anaesthesiologists (ASA) physical status classification grade, baseline SBP at the time of hypotension and pre-surgery HR as covariates (all P < .001). A higher baseline SBP led to a lower absolute increase in MAP. Patients with higher age, higher BMI and lower ASA grade showed smaller increases in MAP. The initial increase was similar for male and female patients. The long-term effect was higher in women. Concomitant antihypertensive medication caused a delayed effect and a lower maximum MAP. The HR increased only slightly (median increase 2.6 bpm, P < .001). CONCLUSIONS: Seven covariates with an impact on the effect of C/T could be identified. The results will enable physicians to optimize the dose with respect to individual patients.

Intraoperative haemodynamic monitoring and management of adults having non-cardiac surgery: Guidelines of the German Society of Anaesthesiology and Intensive Care Medicine in collaboration with the German Association of the Scientific Medical Societies.

Haemodynamic monitoring and management are cornerstones of perioperative care. The goal of haemodynamic management is to maintain organ function by ensuring adequate perfusion pressure, blood flow, and oxygen delivery. We here present guidelines on "Intraoperative haemodynamic monitoring and management of adults having non-cardiac surgery" that were prepared by 18 experts on behalf of the German Society of Anaesthesiology and Intensive Care Medicine (Deutsche Gesellschaft für Anästhesiologie und lntensivmedizin; DGAI).

A randomized open label, parallel-group study to evaluate the hemodynamic effects of Cafedrine/Theodrenaline vs Noradrenaline in the treatment of intraoperative hypotension after induction of general anesthesia: the "HERO" study design and rationale.

OBJECTIVE: Intraoperative arterial hypotension (IOH) is associated with poor patient outcome. This study aims to compare the hemodynamic effects of Cafedrine/Theodrenaline (C/T) and Noradrenaline (NA) for the treatment of hypotension in patients who develop IOH after anesthesia induction. RESEARCH DESIGN AND METHODS: This is a national, randomized, parallel-group, multicenter, and open-label study. Adult patients (≥50 years, ASA-classification III-IV) who undergo elective surgery will be included. When IOH (MAP <70 mmHg) develops, C/T or NA will be given as a bolus injection ("bolus phase", 0-20 min after initial application) and subsequently as continuous infusion ("infusion phase", 21-40 min after initial application) to achieve MAP = 90 mmHg. Hemodynamic data are captured in real time by advanced hemodynamic monitoring. RESULTS: Primary endpoints, i.e. the treatment-related difference in average mean arterial pressure (MAP) during the "infusion phase" and the treatment-related difference in average cardiac index during the "bolus phase" are assessed (fixed-sequence method). Non-inferiority of C/T compared to NA in achieving 90 mmHg (MAP) when applied as continuous infusion is hypothesized. In addition, superiority of C/T over NA, applied as bolus injection, in increasing cardiac index is postulated. It is estimated that 172 patients are required to establish statistical significance with a power of 90%. After adjusting for ineligibility and dropout rate, 220 patients will be screened. CONCLUSION: This clinical trial will yield evidence for marketing authorization of C/T applied as continuous infusion. Additionally, the effects of C/T compared to NA on cardiac index will be assessed. First results of the "HERO"-study are expected in 2024. DRKS identifier: DRKS00028589. EudraCT identifier: 2021-001954-76.

Quantification of exhaled propofol is not feasible during single-lung ventilation using double-lumen tubes: A multicenter prospective observational trial.

BACKGROUND: Volatile propofol can be measured in exhaled air and correlates to plasma concentrations with a time delay. However, the effect of single-lung ventilation on exhaled propofol is unclear. Therefore, our goal was to evaluate exhaled propofol concentrations during single-lung compared to double-lung ventilation using double-lumen tubes. METHODS: In a first step, we quantified adhesion of volatile propofol to the inner surface of double-lumen tubes during double- and single-lumen ventilation in vitro. In a second step, we enrolled 30 patients scheduled for lung surgery in two study centers. Anesthesia was provided with propofol and remifentanil. We utilized left-sided double-lumen tubes to separately ventilate each lung. Exhaled propofol concentrations were measured at 1-min intervals and plasma for propofol analyses was sampled every 20 min. To eliminate the influence of dosing on volatile propofol concentration, exhalation rate was normalized to plasma concentration. RESULTS: In-vitro ventilation of double-lumen tubes resulted in increasing propofol concentrations at the distal end of the tube over time. In vitro clamping the bronchial lumen led to an even more pronounced increase (Δ AUC +62%) in propofol gas concentration over time. Normalized propofol exhalation during lung surgery was 31% higher during single-lung compared to double-lung ventilation. CONCLUSION: During single-lung ventilation, propofol concentration in exhaled air, in contrast to our expectations, increased by approximately one third. However, this observation might not be affected by change in perfusion-ventilation during single-lung ventilation but rather arises from reduced propofol absorption on the inner surface area of the double-lumen tube. Thus, it is only possible to utilize exhaled propofol concentration to a limited extent during single-lung ventilation. REGISTRATION OF CLINICAL TRIAL: DRKS-ID DRKS00014788 (www.drks.de).

Vapocoolant Spray Versus Lidocaine Infiltration for Radial Artery Cannulation: A Prospective, Randomized, Controlled Clinical Trial.

OBJECTIVES: Local infiltration with lidocaine is a frequently used measure to prevent pain during arterial cannulation. Its administration is associated with pain. Vapocoolants like ethyl chloride or alkanes also affect rapid-onset anesthesia. However, their administration causes less discomfort compared with administration of lidocaine. The effectiveness of vapocoolants in mitigating discomfort associated with arterial cannulation never has been studied. The authors therefore compared vapocoolant with lidocaine for reducing discomfort caused by arterial cannulation. DESIGN: Prospective, randomized, controlled study. SETTING: University hospital, single center. PARTICIPANTS: One hundred sixty adult patients requiring arterial cannulation before induction of general anesthesia for cardiac surgery or carotid endarterectomy. INTERVENTIONS: Patients received either lidocaine infiltration or vapocoolant spray prior to arterial cannulation. Overall discomfort resulting from the whole procedure (applying local/topical anesthesia followed by arterial puncture) was rated on a 0 to 10 numerical rating scale. Puncture failure rate and time required for the intervention also were recorded. MEASUREMENTS AND MAIN RESULTS: One hundred forty-three patients were included in the per-protocol analysis. Mean pain scores in the vapocoolant group were 3.4 (±1.58) compared with 4.5 (±2.29) in the lidocaine group (difference 1.1±0.33; p = 0.032; Mann-Whitney U-test). The higher puncture failure rate in the lidocaine group (n = 11 v 4) was not significant (p = 0.06; Fisher's exact test). The time required for the intervention was longer in the lidocaine group (138±44 s v 128±44 s; p = 0.019; Mann-Whitney U-test). CONCLUSIONS: Vapocoolant spray is an alternative to lidocaine infiltration to mitigate discomfort associated with arterial cannulation.

Use of Fentanyl Iontophoretic Transdermal System (ITS) (IONSYS®) in the Management of Patients with Acute Postoperative Pain: A Case Series.

Fentanyl iontophoretic transdermal system (ITS) [IONSYS®, The Medicines Company, Parsippany, NJ, USA] is a needle-free, patient-controlled, postoperative opioid pain management treatment. It is indicated for the short-term management of acute postoperative pain in adults requiring opioid analgesia in the hospital. The safety and effectiveness of fentanyl ITS for acute postoperative pain management has been demonstrated in a range of surgery and patient types studied in seven phase 3 trials (three placebo-controlled trials and four active-comparator trials). The majority of the patients in the phase 3 trials had undergone either abdominal/pelvic, orthopedic, or thoracic surgery. Consistent with the prescribing information, physicians in clinical practice may treat patients with this system following any type of surgery including those that may not have been included in the phase 3 trials. The purpose of this case series is to illustrate how fentanyl ITS is being utilized for postoperative pain management in real-world clinical practice following a variety of surgeries and in current pain management protocols that may have evolved since the completion of the phase 3 program. There are seven cases from three clinical centers described within this case series, each using fentanyl ITS according to the prescribing information. The surgery types included are bariatric (N = 3), prostate (N = 2), colorectal (N = 1), and perirectal abscess drainage (N = 1). A systematic review of each patient chart was conducted via a standardized retrospective assessment by the clinicians who managed each patient. Additionally, each healthcare professional was interviewed regarding their overall experience and key learnings using fentanyl ITS. Overall, fentanyl ITS was effective and well tolerated in these case reports in current-day clinical practice settings. These case studies are informative about fentanyl ITS use shortly after product approval and set the stage for additional clinical research.

Does femoral nerve catheter placement with stimulating catheters improve effective placement? A randomized, controlled, and observer-blinded trial.

Continuous peripheral nerve blocks offer the benefit of extended postoperative analgesia and accelerated functional recovery after major knee surgery. Conventional nerve localization is performed over a stimulating needle followed by blind insertion of the peripheral catheter. Correct catheter placement is confirmed by testing for satisfactory analgesia. Stimulating catheters offer the advantage of verifying correct placement close to the nerve during catheter placement. The aim of this randomized trial was to determine whether accurate catheter positioning under continuous stimulation accelerates the onset of sensory and motor block, improves the quality of postoperative analgesia, and enhances functional recovery. We compared femoral nerve catheters inserted under continuous stimulation with catheters that were placed using the conventional technique of blind advancement in 81 patients undergoing major knee surgery. Time of catheter placement was similar in both groups with 4 min (3/7.3; median, 25th/75th percentile) in the conventional group and 5 min (4/8.8) in the stimulating catheter group. In both groups, 42% of the catheters could be correctly placed (motor response of the patella with a current < or =0.5 mA) at first attempt. In 22 patients (58%) of the stimulating catheter group, the catheter had to be redirected 1-20 times, including 2 that could not be correctly placed within 20 min. The onset time of sensory and motor block was almost similar in both groups. There were no differences in the postoperative IV opioid consumption, and visual analog scale pain scores at rest and movement, or maximal bending and stretching of the knee joint during the 5 days after surgery. We conclude that with continuous femoral nerve blocks, blind catheter advancement is as effective as the stimulating catheter technique with respect to onset time of sensory and motor block as well as for postoperative pain reduction and functional outcome.